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Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Mediated Pulmonary DNA Adducts and Cytochrome P450 (CYP)1B1 by Dietary Antioxidants, Omega-3 Fatty Acids, in Mice
Numerous human and animal studies have reported positive correlation between carcinogen-DNA adduct levels and cancer occurrence. Therefore, attenuation of DNA adduct levels would be expected to suppress tumorigenesis. In this investigation, we report that the antioxidants omega 3-fatty acids, which...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773186/ https://www.ncbi.nlm.nih.gov/pubmed/35052622 http://dx.doi.org/10.3390/antiox11010119 |
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author | Zhou, Guodong Jiang, Weiwu Xia, Guobin Wang, Lihua Richardson, Molly Chu, Chun Moorthy, Bhagavatula |
author_facet | Zhou, Guodong Jiang, Weiwu Xia, Guobin Wang, Lihua Richardson, Molly Chu, Chun Moorthy, Bhagavatula |
author_sort | Zhou, Guodong |
collection | PubMed |
description | Numerous human and animal studies have reported positive correlation between carcinogen-DNA adduct levels and cancer occurrence. Therefore, attenuation of DNA adduct levels would be expected to suppress tumorigenesis. In this investigation, we report that the antioxidants omega 3-fatty acids, which are constituents of fish oil (FO), significantly decreased DNA adduct formation by polycyclic aromatic hydrocarbons (PAHs). B6C3F1 male mice were fed an FO or corn oil (CO) diet, or A/J male mice were pre-fed with omega-3 fatty acids eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA). While the B6C3F1 mice were administered two doses of a mixture of seven carcinogenic PAHs including benzo(a)pyrene (BP), the A/J mice were treated i.p. with pure benzo[a]pyrene (BP). Animals were euthanized after 1, 3, or 7 d after PAH treatment. DNA adduct levels were measured by the (32)P-postlabeling assay. Our results showed that DNA adduct levels in the lungs of mice 7 d after treatment were significantly decreased in the FO or EPA/DHA groups compared with the CO group. Interestingly, both qPCR and Western blot analyses revealed that FO, DHA and EPA/DHA significantly decreased the expression of cytochrome P450 (CYP) 1B1. CYP1B1 plays a critical role in the metabolic activation of BP to DNA-reactive metabolites. qPCR also showed that the expression of some metabolic and DNA repair genes was induced by BP and inhibited by FO or omega-3 fatty acids in liver, but not lung. Our results suggest that a combination of mechanism entailing CYP1B1 inhibition and the modulation of DNA repair genes contribute to the attenuation of PAH-mediated carcinogenesis by omega 3 fatty acids. |
format | Online Article Text |
id | pubmed-8773186 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87731862022-01-21 Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Mediated Pulmonary DNA Adducts and Cytochrome P450 (CYP)1B1 by Dietary Antioxidants, Omega-3 Fatty Acids, in Mice Zhou, Guodong Jiang, Weiwu Xia, Guobin Wang, Lihua Richardson, Molly Chu, Chun Moorthy, Bhagavatula Antioxidants (Basel) Article Numerous human and animal studies have reported positive correlation between carcinogen-DNA adduct levels and cancer occurrence. Therefore, attenuation of DNA adduct levels would be expected to suppress tumorigenesis. In this investigation, we report that the antioxidants omega 3-fatty acids, which are constituents of fish oil (FO), significantly decreased DNA adduct formation by polycyclic aromatic hydrocarbons (PAHs). B6C3F1 male mice were fed an FO or corn oil (CO) diet, or A/J male mice were pre-fed with omega-3 fatty acids eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA). While the B6C3F1 mice were administered two doses of a mixture of seven carcinogenic PAHs including benzo(a)pyrene (BP), the A/J mice were treated i.p. with pure benzo[a]pyrene (BP). Animals were euthanized after 1, 3, or 7 d after PAH treatment. DNA adduct levels were measured by the (32)P-postlabeling assay. Our results showed that DNA adduct levels in the lungs of mice 7 d after treatment were significantly decreased in the FO or EPA/DHA groups compared with the CO group. Interestingly, both qPCR and Western blot analyses revealed that FO, DHA and EPA/DHA significantly decreased the expression of cytochrome P450 (CYP) 1B1. CYP1B1 plays a critical role in the metabolic activation of BP to DNA-reactive metabolites. qPCR also showed that the expression of some metabolic and DNA repair genes was induced by BP and inhibited by FO or omega-3 fatty acids in liver, but not lung. Our results suggest that a combination of mechanism entailing CYP1B1 inhibition and the modulation of DNA repair genes contribute to the attenuation of PAH-mediated carcinogenesis by omega 3 fatty acids. MDPI 2022-01-05 /pmc/articles/PMC8773186/ /pubmed/35052622 http://dx.doi.org/10.3390/antiox11010119 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhou, Guodong Jiang, Weiwu Xia, Guobin Wang, Lihua Richardson, Molly Chu, Chun Moorthy, Bhagavatula Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Mediated Pulmonary DNA Adducts and Cytochrome P450 (CYP)1B1 by Dietary Antioxidants, Omega-3 Fatty Acids, in Mice |
title | Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Mediated Pulmonary DNA Adducts and Cytochrome P450 (CYP)1B1 by Dietary Antioxidants, Omega-3 Fatty Acids, in Mice |
title_full | Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Mediated Pulmonary DNA Adducts and Cytochrome P450 (CYP)1B1 by Dietary Antioxidants, Omega-3 Fatty Acids, in Mice |
title_fullStr | Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Mediated Pulmonary DNA Adducts and Cytochrome P450 (CYP)1B1 by Dietary Antioxidants, Omega-3 Fatty Acids, in Mice |
title_full_unstemmed | Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Mediated Pulmonary DNA Adducts and Cytochrome P450 (CYP)1B1 by Dietary Antioxidants, Omega-3 Fatty Acids, in Mice |
title_short | Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Mediated Pulmonary DNA Adducts and Cytochrome P450 (CYP)1B1 by Dietary Antioxidants, Omega-3 Fatty Acids, in Mice |
title_sort | attenuation of polycyclic aromatic hydrocarbon (pah)-mediated pulmonary dna adducts and cytochrome p450 (cyp)1b1 by dietary antioxidants, omega-3 fatty acids, in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773186/ https://www.ncbi.nlm.nih.gov/pubmed/35052622 http://dx.doi.org/10.3390/antiox11010119 |
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